This proposal continues our study of the measurement of the parameters of the dopamine neurological system, in vivo. In our first grant we have developed the methodology for using radiobrominated p-bromo-spiroperidol as a quantitative imaging agent. In this application we will use the drug to measure changes in dopamine receptor binding in vivo, in cats. We will also extend our development to use the 75Br labelled drug and Positron Emission Tomograph (PET) to measure receptor densities in the caudate nucleus and frontal cortex of monkeys. These latter experiments are also a step towards obtaining the data needed to use the drug for measurements in humans and if experiments are promising we will apply for a supplementary grant to extend the PET studies to human subjects. Our efforts will concentrate on (a) determining the utility of our equilibrium model of receptor binding, (b) comparing measurements during washout of the drug, measurements of saturation levels of the drug, and measurements of displacement of the drug as methods of determining receptor densities, (c) effects of changes in endogenous dopamine content, and (d) changes in receptor densities under long-term treatment with drugs and lesions. Most of these measurements will be compared to results obtained by studies of the animal tissues after each series is completed. Since chronic neuroleptic treatment has been observed to cause behavioral changes in monkeys we will also have the opportunity of observing correlations of changes in receptor density and the onset of rigidity and posturing.